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CAMBRIDGE, MA, United States

Shima Y.,Brandeis University | Sugino K.,Howard Hughes Medical Institute | Hempel C.M.,Brandeis University | Hempel C.M.,Galenea Corporation | And 6 more authors.
eLife | Year: 2016

There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However, since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (enhancertrap.bio.brandeis.edu). © Shima et al.

Galenea Corporation | Entity website

Publications Chan, B, Cottrell, JR, Li, B, Larson, KC, Ashford, CJ, Levenson, JM, Laeng, P, Gerber, DJ, and Song, J. (2013) Development of a High-Throughput AlphaScreen Assay for Modulators of Synapsin I Phosphorylation in Primary Neurons ...

Galenea Corporation | Date: 2010-04-23

The present invention provides, in some aspects, methods for identifying agents useful in treating disorders or conditions associated with cognitive deficits. In some aspects, the invention provides methods for detecting a cognitive deficit in a subject.

Galenea Corporation | Date: 2014-11-04

Indole compounds are disclosed. Also disclosed are methods for using the compounds to treat human and animal disease, pharmaceutical compositions of the compounds, and kits including the compounds.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 699.79K | Year: 2011

DESCRIPTION (provided by applicant): This application, Novel serotonergic, pro-cognitive antipsychotic therapies , is in response to PA-08-142: Pharmacologic Agents and Drugs for Mental Disorders (SBIR [R43/R44]). Schizophrenia is a devastating brain disorder that affects approximately 0.7% of the global population. The symptoms of schizophrenia can be grouped into three major categories: positive (e.g. hallucinations and delusions), negative (e.g. social isolation and inappropriate emotional response),and cognitive symptoms. The cognitive symptoms of schizophrenia include impaired attention and disruption of working memory, an essential type of short term memory. These fundamental cognitive processes are critical for the performance of day-to-day activities, and their disruption in schizophrenia is a key factor underlying the inability of patients to integrate successfully into society. Indeed, the cognitive deficits associated with schizophrenia are recognized as a core component of the disorder. Currently available antipsychotic therapies are effective at ameliorating the positive symptoms of schizophrenia, but they are not effective at treating the negative or cognitive symptoms of the disease. Moreover, these therapies often cause significant side effects such as motor disturbances, weight gain, and diabetes. For these reasons, schizophrenia represents a major area of unmet medical need which must be addressed by the discovery and development of new antipsychotic therapies that are effective at treating the cognitive symptoms of schizophrenia with reduced potential for side effects. The overall goal of this proposal is to optimize a series of lead compounds we have identified with dual 5-HT2C receptor agonist and 5-HT6 receptor antagonist activities. Compounds with this novel pharmacological profile hold promise for yielding safe and effective treatments for the positive as well as the cognitive symptoms of schizophrenia. Such compounds are likely to have a significantly reduced risk for generating the undesirable side effects that are typically observed with currently available antipsychotic therapies. Successful completion of the specific aims outlined in this proposal will result in the identification of lead compounds with desirable pharmacological and drug-like properties. Furthermore, proof-of-concept for this novel target profile will be achieved by demonstrating antipsychotic and pro-cognitive efficacy in animal models with a selected lead compound. These achievements will provide a solid basis fora Phase II SBIR application to support further research aimed at selecting a clinical development candidate for the treatment of schizophrenia and its cognitive symptoms. A clinical development candidate with this novel profile would comprise a valuable asset within the pharmaceutical industry and would provide the basis of a successful commercial outcome for the research program. The research outlined in this proposal will directly benefit patients and their families and caregivers by leading to the discovery of safer and more effective medicines for the treatment of schizophrenia. PUBLIC HEALTH RELEVANCE: We have discovered a series of compounds with a unique target profile for specific serotonin receptors that are relevant to schizophrenia and cognition. Based on this discovery, we are optimizing these compounds to identify a new class of candidate drugs for treatment of schizophrenia and its severe cognitive deficits. Our goal is to discover new therapies that are more effective than current treatments with reduced potential for side effects. This research will thus have a positive impact on the significant population of schizophrenia patients and their family members and caregivers, which includes many millions of people worldwide. In particular,improving the cognitive outcome in schizophrenia will help patients to improve their job performance and to integrate into society more effectively.

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